Hb D-Los Angeles is characterized by the substitution of glutamine for glutamic acid at position 121 of the beta-globin chain. The present investigation is the first study on the beta-globin gene haplotypes associated with beta-D-Los Angeles in Western Iran. Thirty two individuals from 11 unrelated families from Western Iran were studied. The Hb D-Los Angeles status of all cases was confirmed using polymerase chain reaction (PCR) followed by digestion with EcoRl. The haplotype of the beta-globin gene cluster was determined by a PCR-RFLP (restriction fragment length polymorphism) procedure. The haplotype background of the betaA chromosomes was also determined in 35 normal subjects from the same geographic region. The beta-globin gene haplotype analysis demonstrated that all beta-D-Los Angeles genes (23 genes) were in linkage disequilibrium with haplotype I [+----++]. Among the 70 betaA chromosomes, 30 chromosomes (42.9%) were associated with haplotype I. The present study indicates the unicentric origin of the beta-D-Los Angeles gene in Western Iran. It seems that this mutation may have occurred at the same chromosomal background common in the local population.